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Thursday, 2 December 2010

How to breed dogs with stronger immune systems?

Two summers ago, the small rescue I run brought over a black collie cross boy from Ireland. He had landed in Dunboyne pound near Dublin as a stray and never been claimed. We specialise in retrievery crosses and he seemed a nice chap so I was sure we could find a home for him. Deep into researching the evolution of the dog at the time, I called him Darwin.

Like all the dogs that travel from Ireland, he arrived in the very early hours of the morning and it was clear right from the start that he was lovely – sweet, unassuming and affectionate. He trotted a little tentatively into our garden and then started rolling over and over on the grass with delight. Within half an hour he was playing beautifully with our Tickle who takes all the new dogs under her wing.

It was still really early, but my other half Jon who tries to feign disinterest in the new rescues, popped a head out of the bedroom window to have a peek, then came down and made us a cup of tea. We sat down on a step outside to drink it and Darwin came over to plant a kiss on my face. I reached up to stroke him under his neck and found a golf-ball-sized lump. There was one on the other side too - clearly enlarged lymph nodes. I quickly checked and every other lymph node on Darwin’s body was up like a hard rock. My heart sank.

I knew Darwin had been unwell in Ireland – he’d gone down with something in the pound, as many do. But he’d bounced back with antibiotics. I took him to our vets who gave him the once over and then looked up at me with raised eyebrows. “I think it’s lymphoma,” she said confirming what I already knew in my heart. But she gave me some antibiotics and we took him home.

There was no question of us subjecting Darwin to any heroic treatments. The prognosis for lymphoma is poor, even with the most advanced care. It is rare that it can give a dog much more than a few more weeks and we felt this little chap had been through enough without subjecting him to the rigours of chemotherapy.

Darwin was a little star. He fitted in seamlessly with us; he loved his walks, loved his food, loved my dogs and even managed to put on a kilo – yay! In the evening, he’d creep up on to your lap, tuck himself into your neck and sigh, like he was the happiest dog in the world. At night, he would sneak up on to the bed and curl up small. We pretended we didn’t notice.

I allowed myself to hope – a little – that the diagnosis was wrong. But the lumps didn’t go down, and although he was active and playful, when he was in repose, you could tell he wasn’t well. He was also unnaturally hot.

Two weeks after he arrived with us, Darwin was much quieter on his walk. That evening, he ate his supper then went to lie in his favourite spot on a rug in front of the television. His breathing was fast and shallow. I picked him up and laid him back in my arms on the sofa. He snuggled into my chest and closed his eyes. He was baking hot and although he would respond a little if I stroked or talked to him, it was an effort. I knew it was time.

Darwin: ? - 21/6/08

I called the vet and Darwin slipped away, ever-so gently, before, even, the needle was withdrawn from the vein in his leg.Of course one rails against the injustice of a two-year-old dog being taken by cancer. But we also felt blessed by this little man for both the pleasure he gave us and for the sheer joy with which he lived his last two weeks, away from the horrors of an Irish pound and whatever life it was that had led to him landing there.

I tell this story because it is easy to forget that crossbreeds can suffer from horrible diseases like lymphoma too, and not all cancer in purebreds is down to the inheritance of breed-specific cancer genes. But purebred dogs as a whole, according to one recent Italian study, do suffer twice as much cancer as their randomly-bred cousins and some of these cancers are breed specific - as are other canine health issues that we now think are the result of immune systems that have been compromised by inbreeding.

Our immune system is why we don’t die of a cold, or the tiniest of scratches. It is probably the case that all living beings get cancer every second of every day; it’s just that our immune system stamps on it. It is our own personal army of sentinel soldiers who are on the lookout for any breach of your defences. Once spotted, a counter-attack is launched to repel the invader – be it bacteria, virus, parasite or cancer.

An optimum immune system has a large armoury of diverse weapons – different genes – primed to take on the enemy. Inbreeding, however, reduces the number of different weapons at the immune system’s disposal because related individuals are likely to be genetically very similar. It’s a bit like nature’s version of scissors-paper-stone. A mating between close relatives could easily result in a double-dose of scissors – making the progeny invincible against paper, but pretty damn useless against stone.

Inbreeding affects the immune system in another way too: it reduces the ability to distinguish “self” from “enemy”. And that can be deadly. The Tasmanian Devil, for instance, is being decimated by an infectious cancer that the small marsupial’s immune system simply doesn’t see as a foreign invader. Likewise, the immune system might suddenly start attacking its own tissues, wrongly identifying them as an enemy. The result are autoimmune diseases such as Addison’s Disease, atopy, hypothyroidism and various inflammatory disorders

There is some good news, though. Finnish and UK university scientists in collaboration with a private company, Genoscoper, have worked out how to test a key part of the genome involved in coding our immune systems – an area scientists call the ‘major histocompatability complex’. (A bit of a mouthful even for them, though, so it’s shortened to ‘MHC’.) For £150, you can send off a mouth swab from your dog to the Genoscoper lab in Helsinki and back will come a list of the “haplotypes” that make up a part of your dog’s MHC.

What’s a haplotype? It’s simply a bunch of linked genes that are inherited as a group. Just like with single genes, you have pairs of them – one inherited from each parent. It’s been found, for instance, that Salukis have at least 35 different haplotypes across the breed as a whole. Nova Scotia Tolling Retrievers, however, have only five different haplotypes at their disposal in the part of the MHC that Genoscoper tests.

Some haplotypes are associated with specific diseases but, in general, the more haplotypes there are in the breed, the better. In other words, you’d expect Salukis to be healthier than in Tollers. And, indeed, that’s the case. Tollers suffer from a number of serious immune-mediated problems, notably systemic lupus erythemotosis (SLE) and a rheumatic condition named after the breed - Toller Disease.In Bearded Collies, only seven haplotypes have been found and they too suffer a lot of auto-immune problems, including symmetrical lupoid onychodystrophy (SLO) which affects the development of the dogs’ claws.

Whippets, meanwhile, have been found to have 13 haplotypes and are, generally, considered a rather healthier breed.

There are two ways in which the Genoscoper test could be a real help. First, it can be used to get an overall measure of the MHC diversity of a breed. Fifteen forward-thinking breed clubs have already done this and as word spreads, many more are considering it. It’s not cheap because Genoscoper needs 50-100 DNA samples for each breed at a cost of £150 per swab (although Genoscoper will discount for larger numbers). But the result is a genuinely-useful benchmark that breed clubs – and perhaps kennel clubs too – can use to help guide them in planning an overall breeding strategies for a breed. It’s already known, for instance, that some haplotypes are much more common than others. Identifying and breeding from dogs blessed with rare haplotypes could bring in some much-needed diversity to a breed without the need to outcross to a totally different breed.

The second way the Genoscoper test can help is by giving individual breeders a way to produce puppies with the strongest-possible immune systems. How? Well, let’s say a breeder has narrowed the choice of stud dog for her bitch down to three great possibles. The Genoscoper test will allow her to choose the one that has the most different MHC haplotypes – and also allow her to avoid doubling up on haplotypes that are associated with particular health issues (such as SLE in Tollers and SLO in Beardies) in much the same way as a standard DNA test. In fact, studies show that dogs that inherit indentical haplotypes from each parent - even if those haplotpes are not associated with a particular problem - are at an increased risk of auto-immune disorders.

Ironically, the Genoscoper test will never help randomly-bred dogs like sweet Darwin, the victim of an unlucky throw of the dice. And there is much more to understand about how our dogs’ immune systems work - and particularl how it interacts with other genes. Undobutedly, the MHC plays a big role in how dogs deal with various disorders, but it is not the whole story. Even the strongest immune systems may not be able to cope if the genetic dice are really loaded, or if the environmental onslaught is just too great. But I love the idea of the Genoscoper test and the hope it offers.

Geneticists warn us that it will be impossible – and indeed not always desirable – to eradicate all dodgy genes from our dogs even if it was possible to identify them all. So what a wonderful idea it is to approach it from a different angle; to boost our dogs’ immune systems so that they are better able to deal with the various onslaughts that life and genetics throw at them – including those diseases for which at present there are no DNA tests.

This article is reprinted from the August 2010 issue of Dogs Today Magazine. A pdf of the article can be downloaded here . Permission is given for its reproduction (for non-commercial use) as long as myself, Dogs Today and illustrator Kevin Brockbank are credited.

12 comments:

This is why I don't understand some of the arguments against purebred dogs. Sure, breeding so a dog has no face is bad, but I've owned shelter mutts all my life and they all die of cancer sooner or later. It doesn't really matter if a certain breed has more of one type of cancer and less of another if it kills them. 3 members of my family have had at least 1 purebred assistance dog (early onset Parkinsons), and I've never seen nor heard anyone claim that they die earlier than mutts - if there were a huge gap in life expectancy, you'd expect there'd be a lot more interest in finding acceptable crossbreeds for the job. And even if the dogs do suffer a slight disadvantage healthwise, it doesn't outweigh the benefit of knowing that they come from a line that's tested and proven to be able to work for the people that rely on them.

Yes, that's the equation that needs to be done - a certain predictability against less predictability.

We're always, inevitably, influenced by our own experiences, but the wider picture is what we need to look at to be able to see what's going on. Cross/mixed breed dogs do indeed live a little longer on average (lots of studies have now confirmed this) as scientific theory predicts. But of course as I have posted above, it doesn't mean crossbreeds don't get cancer, and many purebred dogs do live long and healthy lives.

The whole essence of this blog, though, is that a) too many don't and b) that it doesn't have to be that way. In other words, many more could lead healthier, longer lives if we changed the way we breed them.

Contrary to what people think, I love all dogs - and that includes pedigree dogs. Nothing makes my heart beat faster than a beautiful flatcoated retriever - it's just that I can't bear the fact that so many die prematurely from cancer and I want more to be done to address it. This doesn't mean just giving money or tissue samples to the researchers; many do that already. It means thinking about broadening the gene pool; perhaps doing a breed-wide DLA diversity; asking owners for more data about their flatcoat cancer deaths so that the researchers have more data. Etc.

Sure, the MHC is important but to promote haplotypes as the answer to all problems is a little irresponsible.

Pity you weren't at the KC Breeders' Symposium last weekend, when you could have heard Cathryn Mellersh (who has contributed just a little to the knowledge of canine genetics!) question the usefulness of relying too much on haplotype testing.

You might want to re-read the article, Sheila - nowhere do I promote haplotype testing as the "answer to all".

And I would agree with Cathryn. Haplotype testing is just one tool - nevertheless a potentially extremely useful one, particularly in a breed such as yours (should there be any MHC diversity remaining in the breed).

The DLA Diversity test, incidentally, was developed by Professor Hannes Lohi at the University of Helskinki. He too has contributed just a little to the knowledge of canine genetics.

Jemima, have you looked at all at the Optimal Selection test, which is designed (per their marketing) to help breeders optimize genetic diversity? Wondering how useful and reliable it actually is, went ahead and used it, but still wondering a bit.

Another reason that selectively bred dogs of any type may be more vulnerable, not only so called 'purebred' dogs, is that we are interfering in the natural process of mate selection which ordinarily maximises immunity. I will explain...

Even humans to a very large extent select a mate by scent; women in particular are very much more or less attracted to a given man based on his scent signature. Turns out, what a woman is picking up on are scent signatures from the man's MHC which indicate to her the degree of compatibility with her own MHC. The man who smells best to a given woman is the one who has the broadest, most opposite MHC, meaning the pair's offspring will have the widest possible spectrum of immunity...um, widgets!

So I imagine that dogs will do this as well, when permitted to freely mate select. They will instinctively favour immunologically optimum mates based on their MHC scent signatures.

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About Me

I grew up with pedigree dogs - English Setters, Great Danes, Labradors and, most recently, Flatcoated Retrievers. Today, I share my home with an assortment of dogs, purebred and mutts. In 2008, I directed Pedigree Dogs Exposed, a BBC documentary which uncovered the extent of health and welfare problems in pedigree dogs. The film has now been shown in more than 20 countries. Campaigning for improved purebred dog health is now a great passion - one fuelled by the fear that those who currently view themselves as the guardians of pedigree dogs are, often unwittingly, the agents of their demise.
My mission, then, is to continue to highlight where things have gone wrong and to encourage breeders and Kennel Clubs to embrace reform - particularly when it comes to harmful phenotypes and inbreeding.